NZ520120A - New octahydro-2H-pyrido[1,2-a]pyrazine compounds, a process for their preparation and pharmaceutical compositions containing them - Google Patents
New octahydro-2H-pyrido[1,2-a]pyrazine compounds, a process for their preparation and pharmaceutical compositions containing themInfo
- Publication number
- NZ520120A NZ520120A NZ520120A NZ52012002A NZ520120A NZ 520120 A NZ520120 A NZ 520120A NZ 520120 A NZ520120 A NZ 520120A NZ 52012002 A NZ52012002 A NZ 52012002A NZ 520120 A NZ520120 A NZ 520120A
- Authority
- NZ
- New Zealand
- Prior art keywords
- formula
- compounds
- pyrido
- octahydro
- linear
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 98
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 16
- 238000002360 preparation method Methods 0.000 title claims description 10
- 230000008569 process Effects 0.000 title claims description 9
- ONHPOXROAPYCGT-UHFFFAOYSA-N 2,3,4,6,7,8,9,9a-octahydro-1h-pyrido[1,2-a]pyrazine Chemical class C1CNCC2CCCCN21 ONHPOXROAPYCGT-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 290
- 238000011282 treatment Methods 0.000 claims abstract description 15
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- 108010002059 Histamine Receptors Proteins 0.000 claims abstract description 9
- 239000005557 antagonist Substances 0.000 claims abstract description 7
- 239000003814 drug Substances 0.000 claims abstract 6
- 238000004519 manufacturing process Methods 0.000 claims abstract 4
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 165
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 56
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 53
- GXWNSJYVSIJRLS-UHFFFAOYSA-N 6-bromo-8-methylimidazo[1,2-a]pyrazine Chemical compound CC1=NC(Br)=CN2C=CN=C12 GXWNSJYVSIJRLS-UHFFFAOYSA-N 0.000 claims description 45
- 125000000217 alkyl group Chemical group 0.000 claims description 42
- 239000000203 mixture Substances 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 27
- -1 cyano, hydroxy Chemical group 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 21
- PXWLUICTRPHECG-UHFFFAOYSA-N azane;trihydrochloride Chemical compound N.Cl.Cl.Cl PXWLUICTRPHECG-UHFFFAOYSA-N 0.000 claims description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 18
- 239000002253 acid Substances 0.000 claims description 18
- 125000005843 halogen group Chemical group 0.000 claims description 16
- 230000003287 optical effect Effects 0.000 claims description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 15
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 14
- 125000002947 alkylene group Chemical group 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 230000002490 cerebral effect Effects 0.000 claims description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 12
- 125000002252 acyl group Chemical group 0.000 claims description 12
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 11
- 125000001072 heteroaryl group Chemical group 0.000 claims description 10
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 claims description 9
- 239000004480 active ingredient Substances 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 238000003786 synthesis reaction Methods 0.000 claims description 8
- 230000009471 action Effects 0.000 claims description 7
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- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 6
- 230000001149 cognitive effect Effects 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 238000000746 purification Methods 0.000 claims description 6
- 239000012312 sodium hydride Substances 0.000 claims description 6
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims description 5
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- 208000000609 Pick Disease of the Brain Diseases 0.000 claims description 4
- 125000004423 acyloxy group Chemical group 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 4
- 230000004770 neurodegeneration Effects 0.000 claims description 4
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 235000020824 obesity Nutrition 0.000 claims description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- 238000000926 separation method Methods 0.000 claims description 4
- 239000007858 starting material Substances 0.000 claims description 4
- 230000002739 subcortical effect Effects 0.000 claims description 4
- 230000002792 vascular Effects 0.000 claims description 4
- 238000004458 analytical method Methods 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 231100000252 nontoxic Toxicity 0.000 claims description 3
- 230000003000 nontoxic effect Effects 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 2
- 125000006557 (C2-C5) alkylene group Chemical group 0.000 claims description 2
- 229910014033 C-OH Inorganic materials 0.000 claims description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- 229910014570 C—OH Inorganic materials 0.000 claims description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 2
- 239000005864 Sulphur Substances 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 125000002619 bicyclic group Chemical group 0.000 claims description 2
- 210000004556 brain Anatomy 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 230000008878 coupling Effects 0.000 claims description 2
- 238000010168 coupling process Methods 0.000 claims description 2
- 238000005859 coupling reaction Methods 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- 229960001760 dimethyl sulfoxide Drugs 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 150000003141 primary amines Chemical class 0.000 claims description 2
- 150000003512 tertiary amines Chemical class 0.000 claims description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims 2
- 238000001061 Dunnett's test Methods 0.000 claims 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims 1
- 229920002472 Starch Polymers 0.000 claims 1
- 238000003556 assay Methods 0.000 claims 1
- 238000003149 assay kit Methods 0.000 claims 1
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- 239000001863 hydroxypropyl cellulose Substances 0.000 claims 1
- 239000008101 lactose Substances 0.000 claims 1
- 235000019359 magnesium stearate Nutrition 0.000 claims 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims 1
- 229940100445 wheat starch Drugs 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 2
- 201000010099 disease Diseases 0.000 abstract 1
- 230000001404 mediated effect Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 84
- 238000004452 microanalysis Methods 0.000 description 79
- 239000000758 substrate Substances 0.000 description 69
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 58
- 239000000243 solution Substances 0.000 description 56
- 238000002844 melting Methods 0.000 description 44
- 230000008018 melting Effects 0.000 description 44
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
- 239000000047 product Substances 0.000 description 34
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 25
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 20
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 19
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000002904 solvent Substances 0.000 description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
- ULTHEAFYOOPTTB-UHFFFAOYSA-N 1,4-dibromobutane Chemical compound BrCCCCBr ULTHEAFYOOPTTB-UHFFFAOYSA-N 0.000 description 16
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 13
- 238000004587 chromatography analysis Methods 0.000 description 11
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
- 229910052786 argon Inorganic materials 0.000 description 10
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 10
- 238000001704 evaporation Methods 0.000 description 10
- 230000008020 evaporation Effects 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
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- 235000011152 sodium sulphate Nutrition 0.000 description 7
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- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 4
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- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 238000011785 NMRI mouse Methods 0.000 description 2
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- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
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- IPWFJLQDVFKJDU-UHFFFAOYSA-N pentanamide Chemical compound CCCCC(N)=O IPWFJLQDVFKJDU-UHFFFAOYSA-N 0.000 description 1
- 238000011458 pharmacological treatment Methods 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- 229940080818 propionamide Drugs 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- RDCFVGPXAHCPPY-UHFFFAOYSA-N pyrazine;dihydrochloride Chemical compound Cl.Cl.C1=CN=CC=N1 RDCFVGPXAHCPPY-UHFFFAOYSA-N 0.000 description 1
- URLLJAVJPAATKX-UHFFFAOYSA-N pyrazine;trihydrochloride Chemical compound Cl.Cl.Cl.C1=CN=CC=N1 URLLJAVJPAATKX-UHFFFAOYSA-N 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000003956 synaptic plasticity Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 230000028016 temperature homeostasis Effects 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
- USFPINLPPFWTJW-UHFFFAOYSA-N tetraphenylphosphonium Chemical compound C1=CC=CC=C1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 USFPINLPPFWTJW-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- XWKHFFLZJISKNH-UHFFFAOYSA-N tri(propan-2-yl)-(3,4,5-trimethoxyphenyl)sulfanylsilane Chemical compound COC1=CC(S[Si](C(C)C)(C(C)C)C(C)C)=CC(OC)=C1OC XWKHFFLZJISKNH-UHFFFAOYSA-N 0.000 description 1
- CPKHFNMJTBLKLK-UHFFFAOYSA-N tri(propan-2-yl)-sulfanylsilane Chemical compound CC(C)[Si](S)(C(C)C)C(C)C CPKHFNMJTBLKLK-UHFFFAOYSA-N 0.000 description 1
- ZRDDDFSCPLPNTF-UHFFFAOYSA-N tributyl-(3,4,5-trimethoxyphenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC(OC)=C(OC)C(OC)=C1 ZRDDDFSCPLPNTF-UHFFFAOYSA-N 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Neurology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Hospice & Palliative Care (AREA)
- Diabetes (AREA)
- Child & Adolescent Psychology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0109260A FR2827288B1 (fr) | 2001-07-12 | 2001-07-12 | Nouveaux derives d'octahydro-2h-pyrido[1,2-a]pyrazine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ520120A true NZ520120A (en) | 2004-03-26 |
Family
ID=8865405
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ520120A NZ520120A (en) | 2001-07-12 | 2002-07-11 | New octahydro-2H-pyrido[1,2-a]pyrazine compounds, a process for their preparation and pharmaceutical compositions containing them |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US6992085B2 (de) |
| EP (1) | EP1275647B1 (de) |
| JP (1) | JP3950018B2 (de) |
| KR (1) | KR100485020B1 (de) |
| CN (1) | CN1197863C (de) |
| AR (1) | AR036166A1 (de) |
| AT (1) | ATE254124T1 (de) |
| AU (1) | AU2002300094B2 (de) |
| BR (1) | BR0202681A (de) |
| CA (1) | CA2394027C (de) |
| DE (1) | DE60200089T2 (de) |
| DK (1) | DK1275647T3 (de) |
| EA (1) | EA005160B1 (de) |
| ES (1) | ES2210219T3 (de) |
| FR (1) | FR2827288B1 (de) |
| HK (1) | HK1050682A1 (de) |
| HU (1) | HUP0202282A3 (de) |
| MX (1) | MXPA02006699A (de) |
| NO (1) | NO322966B1 (de) |
| NZ (1) | NZ520120A (de) |
| PL (1) | PL355034A1 (de) |
| PT (1) | PT1275647E (de) |
| SI (1) | SI1275647T1 (de) |
| TR (1) | TR200302001T4 (de) |
| ZA (1) | ZA200205596B (de) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004089410A1 (ja) * | 2003-04-03 | 2004-10-21 | Kyowa Hakko Kogyo Co., Ltd. | 神経因性疼痛の予防及び／または治療剤 |
| MY141255A (en) * | 2003-12-11 | 2010-03-31 | Memory Pharm Corp | Phosphodiesterase 4 inhibitors, including n-substituted diarylamine analogs |
| FR2866647B1 (fr) * | 2004-02-20 | 2006-10-27 | Servier Lab | Nouveaux derives azabicycliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| WO2006000914A1 (en) * | 2004-06-22 | 2006-01-05 | Pfizer Products Inc. | Diazabicyclic histamine-3 receptor antagonists |
| JP5121707B2 (ja) * | 2005-07-04 | 2013-01-16 | ハイ ポイント ファーマシューティカルズ，エルエルシー | 新規医薬 |
| RU2442775C2 (ru) * | 2005-07-04 | 2012-02-20 | Хай Пойнт Фармасьютикалс, ЛЛС | Антагонисты гистаминовых н3-рецепторов |
| WO2007106349A2 (en) * | 2006-03-10 | 2007-09-20 | Neurogen Corporation | Piperazinyl oxoalkyl tetrahydroisoquinolines and related analogues |
| KR100871691B1 (ko) | 2006-10-16 | 2008-12-05 | 삼성전자주식회사 | 병렬 비트 테스트 방법 및 그 방법을 사용하는 반도체메모리 장치 |
| EP3495363B1 (de) | 2016-07-28 | 2023-08-23 | Shionogi & Co., Ltd | Stickstoffhaltige kondensierte ringverbindungen mit antagonistischer dopamin-d3-rezeptor-wirkung |
| TW201938537A (zh) | 2018-01-26 | 2019-10-01 | 日商鹽野義製藥股份有限公司 | 具有多巴胺ｄ３受體拮抗作用的稠環化合物 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3388128A (en) * | 1965-09-03 | 1968-06-11 | Allan R. Day | Substituted 1, 4-diazabicyclo [4. 4. 9] decanes |
| GB8518236D0 (en) * | 1985-07-19 | 1985-08-29 | Beecham Group Plc | Compounds |
| WO1994006794A1 (en) * | 1992-09-24 | 1994-03-31 | National Institutes Of Health | Aralkyl diazabicycloalkane derivatives for cns disorders |
| US6231833B1 (en) * | 1999-08-05 | 2001-05-15 | Pfizer Inc | 2,7-substituted octahydro-1H-pyrido[1,2-A]pyrazine derivatives as ligands for serotonin receptors |
| US5731307A (en) * | 1994-09-30 | 1998-03-24 | Pfizer, Inc. | Neuroleptic 2,7-disubtituted perhydro-1h-pyrido 1, 2-A!pyrazines |
| EP1202976B1 (de) * | 1999-07-19 | 2006-11-02 | Merck Frosst Canada Ltd. | Pyrazinone, diese verbindungen enthaltende zusammenstellungen |
-
2001
- 2001-07-12 FR FR0109260A patent/FR2827288B1/fr not_active Expired - Fee Related
-
2002
- 2002-07-05 MX MXPA02006699A patent/MXPA02006699A/es active IP Right Grant
- 2002-07-10 JP JP2002201793A patent/JP3950018B2/ja not_active Expired - Fee Related
- 2002-07-11 ES ES02291745T patent/ES2210219T3/es not_active Expired - Lifetime
- 2002-07-11 SI SI200230005T patent/SI1275647T1/xx unknown
- 2002-07-11 BR BR0202681-3A patent/BR0202681A/pt not_active IP Right Cessation
- 2002-07-11 TR TR2003/02001T patent/TR200302001T4/xx unknown
- 2002-07-11 AT AT02291745T patent/ATE254124T1/de not_active IP Right Cessation
- 2002-07-11 PT PT02291745T patent/PT1275647E/pt unknown
- 2002-07-11 NO NO20023345A patent/NO322966B1/no not_active IP Right Cessation
- 2002-07-11 NZ NZ520120A patent/NZ520120A/en unknown
- 2002-07-11 DK DK02291745T patent/DK1275647T3/da active
- 2002-07-11 EP EP02291745A patent/EP1275647B1/de not_active Expired - Lifetime
- 2002-07-11 EA EA200200663A patent/EA005160B1/ru not_active IP Right Cessation
- 2002-07-11 DE DE60200089T patent/DE60200089T2/de not_active Expired - Fee Related
- 2002-07-12 CA CA002394027A patent/CA2394027C/fr not_active Expired - Fee Related
- 2002-07-12 KR KR10-2002-0040727A patent/KR100485020B1/ko not_active IP Right Cessation
- 2002-07-12 AU AU2002300094A patent/AU2002300094B2/en not_active Ceased
- 2002-07-12 AR ARP020102607A patent/AR036166A1/es unknown
- 2002-07-12 CN CNB021241481A patent/CN1197863C/zh not_active Expired - Fee Related
- 2002-07-12 ZA ZA200205596A patent/ZA200205596B/xx unknown
- 2002-07-12 HU HU0202282A patent/HUP0202282A3/hu unknown
- 2002-07-12 US US10/195,019 patent/US6992085B2/en not_active Expired - Fee Related
- 2002-07-12 PL PL02355034A patent/PL355034A1/xx not_active Application Discontinuation
-
2003
- 2003-04-17 HK HK03102800A patent/HK1050682A1/xx not_active IP Right Cessation
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Legal Events
| Date | Code | Title | Description |
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| PSEA | Patent sealed | ||
| RENW | Renewal (renewal fees accepted) |